A mathematical model of serotype replacement in pneumococcal carriage following vaccination

Abstract

A number of childhood vaccination programmes have recently introduced vaccination against Streptococcus pneumoniae, the pneumococcus, a major cause of pneumonia and meningitis. The pneumococcal conjugate vaccines (PCVs) that are currently in use only protect against some serotypes of the bacterium, and there is now strong evidence that those serotypes not included in the vaccine increase in prevalence among most vaccinated populations. We present a mathematical model for the dynamics of nasopharyngeal carriage of S. pneumoniae that allows for carriage with multiple serotypes. The model is used to predict the prevalence of vaccine type (VT) and non-VT (NVT) serotypes following the introduction of PCV. Parameter estimates for the model are obtained by maximum likelihood using pre-vaccination data from The Gambia. The model predicts that low (1, 6A and 9V) and medium (4, 5, 7F, 14, 18C, 19A and 19F) prevalence serotypes can be eliminated through vaccination, but that the overall prevalence of carriage will be reduced only slightly because of an increase in the prevalence of NVT serotypes. Serotype replacement will be sequential, with high and medium prevalence NVT serotypes dominating initially, followed by an increase of serotypes of low prevalence. We examine the impact of a hypothetical vaccine that provides partial protection against all serotypes, and find that this reduces overall carriage, but is unable to eliminate low or medium prevalence serotypes.

Pneumococcal carriage in rural Gambia prior to the introduction of pneumococcal conjugate vaccine: a population‐based survey

“…Supporting the observed data is a modelling study which predicts that vaccination of small proportions of children will not affect the distribution of serotypes circulating in the population , particularly since the effect on carriage of one dose of PCV7 lasts for <13 months . The absence of serotype replacement, prior to the routine use of PCV, is further supported by data from invasive disease surveillance in the under 5 years age group which shows similar coverage of PCV13 serotypes (80%) in 1989–1991 and at the time of our study (G. Mackenzie, personal communication, 2015).…”

Determinants of high residual post-PCV13 pneumococcal vaccine type carriage in Blantyre, Malawi: a modelling study

“…All have been demonstrated to be highly protective against 7, 10 or 13 common pneumococcal serotypes associated with carriage and disease (also termed vaccine serotypes, VT). A frequently observed consequence of PCV introduction is the increase in both carriage and disease of non-VT pneumococci (NVT), likely due to increased niche availability and reduction of competition between VT and NVT [4][5][6][7][8][9] .…”

“…However, recently published data on nasopharyngeal carriage as measured in a cross-sectional observational study in Blantyre (Southern Malawi), four to seven years after PCV13 introduction (2015)(2016)(2017)(2018), has shown that vaccine impact (VT carriage reduction) has been slower than expected and heterogeneous across age-groups 22 . Epidemiological mathematical models have previously been employed successfully to improve our understanding of pneumococcal dynamics 5,9,[23][24][25][26][27] , as well as having contributed to explain, estimate and project PCV impact 8,11,28 . The main advantage of models is their cost-free potential to test hypotheses and gain a mechanistic, ecological and immunological understanding of carriage and disease dynamics, estimating epidemiological parameters which are difficult to otherwise quantify from raw epidemiological data.…”

“…The main advantage of models is their cost-free potential to test hypotheses and gain a mechanistic, ecological and immunological understanding of carriage and disease dynamics, estimating epidemiological parameters which are difficult to otherwise quantify from raw epidemiological data. For example, models have successfully yielded estimates of VT and non-VT pneumococci transmission potentials 26,[29][30][31] , pneumococcal competition factors 8,9,23,28,32,33 and measures of vaccine-induced protection from carriage at the individual level 11,17,28,34,35 , none of which are readily observed or quantified in crosssectional observational studies.…”

Optimal Serotype Compositions for Pneumococcal Conjugate Vaccination under Serotype Replacement

“…To date, dynamic models have been used in describing pneumococcal transmission, serotype competition as the mechanism of replacement and the net effectiveness of vaccination [7]–[9]. In addition, statistical models utilising serotype-specific carriage data and estimates of invasiveness (probability of disease per carriage episode) have been applied to predict post-vaccination disease patterns [10]–[12].…”